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Biomedical subjects

Pierre Laurent

Publications and source records attributed to Pierre Laurent.

18 recordsLinked to original sources

Kinetic modeling of the polymer-derived ceramics route: investigation of the thermal decomposition kinetics of poly[B-(methylamino)borazine] precursors into boron nitride.

A complete kinetic modeling of the polymer-derived ceramics (PDCs) route is achieved for the first time through the investigation of the solid-state decomposition of a typical melt-spinnable poly[B-(methylamino)borazine] into boron nitride fibers at various heating rates. Through the use of the Lorentz fitting approach, it is shown that the two-step weight loss associated with the polymer-to-ceramic conversion is governed by a complex interplay of five diffusion-type transport mechanisms that are independent of the applied heating schedule. The application of the Friedman method to dynamic thermogravimetry data yields Ea and ln A values that are seen to increase with the extent of the ceramic conversion from region one (Ea = 38.73 kJ mol(-1)) to region five (Ea = 146.64 kJ mol(-1)). This fact indicates that both the mechanisms within those regions are parallel routes to the formation of the final solid-state material and their complexity increases with the conversion progress. The cross-linking process (first weight loss) of the polymer is governed by three dependent poorly energetic mechanisms. The first weight loss is activated by ammonolysis reactions that provide a modified polymer capable of undergoing condensation reactions in regions two and three to yield a highly cross-linked polymer. A large evolution of methylamine is identified during this process. Mineralization (region four) and ceramization (region five) steps are represented by two highly energetic multistep mechanisms. The mineralization step is associated with a large evolution of methylamine and occurs during the transition between the cross-linking and ceramization processes through the cleavage of the inter-ring B-N bonds. Ceramization represents the end of the polymer-to-ceramic conversion in which the planar consolidation of BN hexagons occurs through complex structural rearrangements of the borazine units (cleavage of the intraring B-N bonds) accompanied with an ammonia evolution. Finally, the simulation of the polymer-to-ceramic conversion was demonstrated through a simplified model that appropriately predicted experimental data.

Journal Article↗

Appearance of cuboidal cells in relation to salinity in gills of Fundulus heteroclitus, a species exhibiting branchial Na+ but not Cl- uptake in freshwater.

Fundulus heteroclitus (killifish) is a model organism for ionoregulatory studies, particularly because of its opercular epithelium, although the gills are the major sites of ion exchange. Whereas Na+ and Cl- are excreted through the gills in seawater (SW), the killifish is unusual in taking up only Na+ and not Cl- at the gills in freshwater (FW). We describe morphological changes in the branchial epithelium following transfer from an acclimation medium of 10% SW to 100% SW or FW. In 10% SW, mitochondria-rich cells resemble typical seawater chloride cells (SWCCs) with accessory cells. After transfer to 100% SW, no change occurs in pavement cell (PVC) morphology or mitotic rate (measured by bromo-deoxyuridine technique), although the density of SWCC apertures increases several fold because of the uncovering of buried SWCCs by PVCs, in accord with increased rates of Na+ and Cl- efflux. After transfer to FW, PVC morphology remains unchanged, but SWCCs and accessory cells are quickly covered by PVCs, with many undergoing apoptosis or necrosis. The mitotic rate doubles by 10-14 h but typical freshwater chloride cells (FWCCs) do not appear. Instead, a wedge-shaped cell type that is moderately rich in apically oriented mitochondria, with a large ovoid nucleus, thin cytoplasmic layer, paucity of vesicular-tubular network, and variably villous surface rapidly (by 3 h) and progressively appears in the filament epithelium, by both uncovering and mitosis. This cell type is similar to that recently identified as the site of Na+ uptake in the FW trout gill. We propose the new term "cuboidal cell" for this cell, based on its morphology, to avoid confusion with traditional terminology (of PVC). We hypothesize that the cuboidal cells are the sites of active Na+ uptake in FW F. heteroclitus and suggest that the lack of Cl- uptake is attributable to the absence of typical FWCCs previously described in teleosts.

Adaptation, Physiological↗

Chiral oxime ethers in asymmetric synthesis. O-(1-Phenylbutyl)benzyloxyacetaldoxime, a versatile reagent for the asymmetric synthesis of protected 1,2-aminoalcohols, alpha-amino acid derivatives, and 2-hydroxymethyl nitrogen heterocycles including iminosugars.

Addition of a range of organolithium and Grignard reagents to (E)-O-(1-phenylbutyl)benzyloxyacetaldoxime 1 in the presence of boron trifluoride diethyl etherate is highly diastereoselective. The resulting hydroxylamines undergo N-O bond cleavage upon treatment with zinc-acetic acid or molybdenum hexacarbonyl to give, after N-protection, protected 1,2-aminoalcohols 3 in high enantiomeric purity. Debenzylation of 3a and 3d gave N-Boc (R)-alaninol and (S)-phenylalaninol respectively. The hydroxylamines 2 also serve as alpha-amino acid precursors, 2i being converted into N-formyl-(R)-alaninyl-(S)-(4-bromo)phenylalanine ester 7, the N-terminal dipeptide of a natural depsipeptide. The versatility of the 1,2-aminoalcohol derivatives was further illustrated by their conversion into 5-, 6- and 7-membered 2-hydroxymethyl nitrogen heterocycles 15-19 in high enantiomeric excess by a ring-closing metathesis reaction. Further reaction of the dihydropyrrole 15 gave the iminosugar 1,4-dideoxy-1,4-imino-D-ribitol.

Amino Acids↗

Na+ versus Cl- transport in the intact killifish after rapid salinity transfer.

Much of the early research elucidating the general mechanisms of euryhalinity was performed on the common killifish. More recently, its opercular epithelium with abundant mitochondria-rich cells has proven to be a powerful model for analyzing the mechanisms of active NaCl transport under Ussing conditions in vitro (i.e., with isotonic saline on both surfaces, at short-circuit). However, it is unclear whether this preparation duplicates the gill under real world conditions-i.e., at open-circuit, with real seawater (SW) or freshwater (FW) on the mucosal surface. There have been only limited studies, mostly about 35 years ago, on ion transport in the intact killifish. Therefore, using radioisotopes (22Na, 36Cl), we developed and evaluated methods for the independent measurement of unidirectional Na(+) and Cl(-) influx and efflux rates and internal pools in intact killifish acclimated to 10% SW and abruptly transferred to either 100% SW or FW. Internal Na(+) pools were disturbed less than internal Cl(-) pools by transfer, and were corrected after 3 days in 100% SW or 7 days in FW. Influx and efflux rates in 10% SW were about 3000 micromol kg(-1) h(-1) and increased to 15,000-18,000 micromol kg(-1) h(-1) after transfer to 100% SW, remaining approximately equal and equimolar for Na(+) and Cl(-), and stable from 0.5 to 7 days post-transfer. After transfer to FW, Na(+) influx and efflux rates dropped to 1000-1500 micromol kg(-1) h(-1), with efflux slightly exceeding influx, and remained approximately stable from 0.5 to 7 days. However, while Cl(-) efflux responded similarly, Cl(-) influx rate dropped immediately to negligible values (20-50 micromol kg(-1) h(-1)) without recovery through 7 days. These results differ from early ion transport data in 100% SW, and demonstrate that fluxes stabilize quickly after salinity transfer. They also show that the intact animal responds more quickly than the epithelium, provide qualitative but not quantitative support for the opercular epithelium as a model for the gill under real world SW conditions, and no support for its use as a gill model under real world FW conditions, where branchial Cl(-) uptake is negligible.

Adaptation, Physiological↗

Asymmetric synthesis of N-protected amino acids by the addition of organolithium carboxyl synthons to ROPHy/SOPHy-derived aldoximes and ketoximes.

A new asymmetric synthesis of alpha-amino acids is described in which the key step is the highly diastereoselective addition of organolithium carboxyl synthons (2-furyllithium, phenyllithium, vinyllithium) to (R)- and (S)-O-(1-phenylbutyl) oximes to give hydroxylamines, with vinyllithium being the most satisfactory nucleophilic reagent. Subsequent reductive cleavage of the N-O bond in hydroxylamines, followed by N-protection, and oxidative cleavage of the carboxyl precursor gave a range of N-protected amino acids and esters. The method was exemplified by the synthesis of a range of derivatives of non-proteinogenic amino acids such as 4-bromophenylalanine, tert-leucine, norvaline, cyclohexyl- and aryl-glycines, 2-amino-8-oxodecanoic acid (Aoda) and alpha-methylvaline.

Amines↗

Heart rate and pulse pressure amplification in hypertensive subjects.

BACKGROUND: Although mean blood pressure (MBP) remains unmodified along the arterial tree, pulse pressure (PP) increases physiologically from the central to the peripheral arteries. Amplification of PP is known to be influenced by heart rate (HR), but the impact of this alteration has never been tested in patients with hypertension. METHODS: A total of 712 hypertensive subjects, either treated or untreated, were divided into three classes of HR level. Carotid and brachial systolic blood pressure (SBP), carotid augmentation index, a marker of wave reflections, and carotid-brachial PP amplification were measured using applanation tonometry. RESULTS: Independent of age, sex, and antihypertensive drugs, subjects with HR >80 beats/min were characterized, in comparison with those with lower HR, by reduced carotid SBP, PP, and augmentation index, resulting in a significant increase in PP amplification. In men but not in women, this pattern was associated with higher values of brachial SBP and DBP and by higher incidences of elevated glycemia and atherosclerotic alterations. In the male population, PP amplifications was, independent of HR, associated with the presence of beta blocking agents (negative association) and elevated plasma glucose. CONCLUSIONS: Hypertensive men and women with high HR have significant PP amplifications, principally because of reduced central SBP and disturbed wave reflections. beta-blocking agents and plasma glucose independently alter PP amplification in men but not in women. Whether these opposite patterns influence the gender difference in cardiovascular risk should be prospectively studied.

Adolescent↗

Observations of the intestinal mucosa using environmental scanning electron microscopy (ESEM); comparison with conventional scanning electron microscopy (CSEM).

In order to evaluate the potential use of environmental scanning electron microscopy (ESEM) in biology, structural changes of the jejunal villi of rats were studied after periods of fasting and refeeding, using a conventional scanning electron microscope (CSEM) and ESEM. While observation using the CSEM, involves chemical fixation, drying and coating, observation of fresh, unprepared materials can be directly realized with the ESEM. Environmental microscopy provides a relatively new technology for imaging hydrated materials without specimen preparation and conductive coating. Direct observation of biological samples in their native state is therefore possible with an ESEM. After fasting, the jejunal mucosa is dramatically reduced in size, splits and holes appearing at the tip of the villi. These changes were observed whatever the type of technique used. Artifacts due to the sample preparation for CSEM observation (drying, coating) can therefore be excluded. However, CSEM and ESEM must be used jointly. While, CSEM must be preferred for surface analysis involving high magnifications, ESEM observation, on the other hand, can prove valuable for determining the living aspect of the samples.

Animals↗

Physiological adaptations of the gut in the Lake Magadi tilapia, Alcolapia grahami, an alkaline- and saline-adapted teleost fish.

We describe the gut physiology of the Lake Magadi tilapia (Alcolapia grahami), specifically those aspects associated with feeding and drinking while living in water of unusually high carbonate alkalinity (titratable base=245 mequiv l(-1)) and pH (9.85). Drinking of this highly alkaline lake water occurs at rates comparable to or higher than those seen in marine teleosts. Eating and drinking take place throughout the day, although drinking predominates during hours of darkness. The intestine directly intersects the esophagus at the anterior end of the stomach forming a 'T', and the pyloric sphincter, which comprises both smooth and striated muscle, is open when the stomach is empty and closed when the stomach is full. This unique configuration (a functional trifurcation) allows imbibed alkaline water to bypass the empty stomach, thereby avoiding a reactive mixing with acidic gastric fluids, and minimizes interference with a full stomach. No titratable base was present in the stomach, where the mean pH was 3.55, but the intestine was progressively more alkaline (foregut 6.96, midgut 7.74, hindgut 8.12, rectum 8.42); base levels in the intestinal fluid were comparable to those in lake water. The gut was highly efficient at absorbing water (76.6%), which accompanied the absorption of Na(+) (78.5%), titratable base (80.8%), and Cl(-) (71.8%). The majority of Na(+), base and water absorption occurred in the foregut by an apparent Na(+) plus base co-transport system. Overall, more than 70% of the intestinal flux occurred via Na(+) plus base co-transport, and less than 30% by Na(+) plus Cl(-) co-transport, a very different situation from the processes in the intestine of a typical marine teleost.

Adaptation, Physiological↗

Pulsatile urea excretion in the gulf toadfish: mechanisms and controls.

Opsanus beta expresses a full complement of ornithine-urea cycle (OUC) enzymes and is facultatively ureotelic, reducing ammonia-N excretion and maintaining urea-N excretion under conditions of crowding/confinement. The switch to ureotelism is keyed by a modest rise in cortisol associated with a substantial increase in cytosolic glutamine synthetase for trapping of ammonia-N and an upregulation of the capacity of the mitochondrial OUC to use glutamine-N. The entire day's urea-N production is excreted in 1 or 2 short-lasting pulses, which occur exclusively through the gills. The pulse event is not triggered by an internal urea-N threshold, is not due to pulsatile urea-N production, but reflects pulsatile activation of a specific branchial excretion mechanism that rapidly clears urea-N from the body fluids. A bidirectional facilitated diffusion transporter, with pharmacological similarity to the UT-A type transporters of the mammalian kidney, is activated in the gills, associated with an increased trafficking of dense-cored vesicles in the pavement cells. An 1814 kB cDNA ('tUT') coding for a 475-amino acid protein with approximately 62% homology to mammalian UT-A's has been cloned and facilitates phloretin-sensitive urea transport when expressed in Xenopus oocytes. tUT occurs only in gill tissue, but tUT mRNA levels do not change over the pulse cycle, suggesting that tUT regulation occurs at a level beyond mRNA. Circulating cortisol levels consistently decline prior to a pulse event and rise thereafter. When cortisol is experimentally clamped at high levels, natural pulse events are suppressed in size but not in frequency, an effect mediated through glucocorticoid receptors. The cortisol decline appears to be permissive, rather than the actual trigger of the pulse event. Fluctuations in circulating AVT levels do not correlate with pulses; and injections of AVT (at supraphysiological levels) elicit only minute urea-N pulses. However, circulating 5-hydroxytryptamine (5-HT) levels fluctuate considerably and physiological doses of 5-HT cause large urea-N pulse events. When the efferent cranial nerves to the gills are sectioned, natural urea pulse events persist, suggesting that direct motor output from the CNS to the gill is not the proximate control.

Adaptation, Physiological↗

Influence of sex on the relation between heart rate and aortic stiffness.

BACKGROUND: Heart rate and aortic pulse wave velocity (PWV) are both cardiovascular risk factors. The aim of this study was to evaluate the influence of sex on the heart rate-PWV relationship in two populations of normotensive and hypertensive men and women. PATIENTS AND METHODS: In a first study, steady-state data describing the heart rate-PWV relationship were determined in 558 normotensive men, 308 normotensive women, 323 hypertensive men and 93 hypertensive women. In a second study, the changes in blood pressure and PWV under atrial pacing at 60, 80 and 100 beats/min were investigated in 15 men and 15 women who were either normotensive or hypertensive. RESULTS: In women in study 1, 26.8% of PWV variance in normotensive patients and 15.4% of PWV variance in hypertensive patients was explained by a multiple regression including only age and systolic blood pressure as covariates. In men in study 1, 27% of PWV variance in normotensive patients and 28.5% of PWV variance in hypertensive patients was explained by a multiple regression including age, systolic blood pressure, weight, and also heart rate, as covariates. In study 2, atrial pacing in the overall population tended to decrease mean blood pressure (P = 0.05) and increase pulse pressure (P = 0.003), with no substantial change in PWV. However, when heart rate increased, PWV tended to decrease in women and to increase in men (interaction: P = 0.07).CONCLUSION Accelerated heart rate influences PWV in both normotensive and hypertensive men and, through this mechanism, could influence cardiovascular risk. However, heart rate does not influence PWV in women.

Adult↗

Structural and hemodynamic analysis of the mouse retinal microcirculation.

PURPOSE: In the holangiotic retina, little is known about the connections between and the circulation within microvessel layers. The goal of the present study was to explore the three-dimensional arrangement and hemodynamics of mouse retinal microvessels. METHODS: Confocal microscopy was performed on fluorescein dextran-filled retinal flatmounts. Capillary velocity in the deep layer was measured by epifluorescence intravital microscopy. The changes in the studied parameters after branch retinal vein occlusion were evaluated. RESULTS: The superficial and intermediate layers are both asymmetric crossroads for capillary blood flow, with approximately 70% of the capillary connections directing the flow from the arterioles into the deep layer. The venous flow from the deep layer joins the major veins in the superficial layer through transverse venules, indicating that major veins are directly connected to the deep layer. Red and white blood cell velocities +/- SD in the deep layer were 1.26 +/- 0.34 and 0.8 +/- 0.32 mm/sec respectively. After branch vein occlusion, venule dilation and decreased velocity were observed in the deep layer. CONCLUSIONS: In the mouse retina, a tridimensional model of retinal microcirculation was established, showing that most microvessel connections on the arteriolar side direct the flow from the superficial to the deep layer, and vice versa on the venular side. However, the presence of direct arteriovenous connections in the superficial layer and the longer vessel length in the deep layer offer the possibility of actively modulating intraretinal flow. Compared with other capillary beds, both the capillary velocity and microhematocrit are high, a situation that favors nutrient delivery to the inner retina.

Animals↗

Fish gill morphology: inside out.

In this short review of fish gill morphology we cover some basic gross anatomy as well as in some more detail the microscopic anatomy of the branchial epithelia from representatives of the major extant groups of fishes (Agnathans, Elasmobranchs, and Teleosts). The agnathan hagfishes have primitive gill pouches, while the lampreys have arch-like gills similar to the higher fishes. In the lampreys and elasmobranchs, the gill filaments are supported by a complete interbranchial septum and water exits via external branchial slits or pores. In contrast, the teleost interbranchial septum is much reduced, leaving the ends of the filaments unattached, and the multiple gill openings are replaced by the single caudal opening of the operculum. The basic functional unit of the gill is the filament, which supports rows of plate-like lamellae. The lamellae are designed for gas exchange with a large surface area and a thin epithelium surrounding a well-vascularized core of pillar cell capillaries. The lamellae are positioned for the blood flow to be counter-current to the water flow over the gills. Despite marked differences in the gross anatomy of the gill among the various groups, the cellular constituents of the epithelium are remarkably similar. The lamellar gas-exchange surface is covered by squamous pavement cells, while large, mitochondria-rich, ionocytes and mucocytes are found in greatest frequency in the filament epithelium. Demands for ionoregulation can often upset this balance. There has been much study of the structure and function of the branchial mitochondria-rich cells. These cells are generally characterized by a high mitochondrial density and an amplification of the basolateral membrane through folding or the presence of an intracellular tubular system. Morphological subtypes of MRCs as well as some methods of MRC detection are discussed.

Adaptation, Physiological↗

Low molecular weight heparins: a guide to their optimum use in pregnancy.

The incidence of pulmonary embolism (PE) and venous thromboembolism (VTE) is higher in pregnant patients than in non-pregnant patients. The incidence of thrombosis in all pregnancies is reported to be between 0.05 and 1%, and an incidence as high as 3% may be present in women after caesarean section. Anticoagulant medication is prescribed during pregnancy in patients presenting with VTE, thrombophilia abnormalities, or a history of PE or VTE. Since unfractionated heparin (UH) does not cross the placental barrier, it has become the gold standard anticoagulant therapy during pregnancy. Oral anticoagulants may also be prescribed during the second trimester but they cross the placental barrier. Low molecular weight heparins (LMWH) are effective, easy to use and have good safety profiles. The practical conditions of use have yet to be validated for pregnancy settings. In the absence of an approved indication, LMWH use during pregnancy is therefore the responsibility of the practitioner. However, several studies on LMWH as prophylaxis for PE or VTE have shown that such products are effective with good safety. Moreover, LMWH use is associated with reduced frequencies of thrombocytopenia and osteoporosis compared with UH use. Very few studies on LMWH use for the treatment of PE or VTE during pregnancy have been published, but the safety of LMWH use in this setting appears to be good. The review of the use of LMWH in pregnancy settings includes recommendations on the practical conditions of use. In the absence of large-scale, randomised, double-blind trials in such settings (which are needed), we propose the use of LMWH as prophylaxis for PE and VTE during pregnancy, but not for the treatment of these conditions. In prophylaxis settings, dalteparin sodium and enoxaparin sodium have been the most widely studied LMWH and we believe that priority should therefore be given to those products. Pending approval of LMWH for use in pregnancy, the use of LMWH off-label is the practitioner's responsibility.

Bone Diseases, Metabolic↗

Obligatory urea production and the cost of living in the Magadi tilapia revealed by acclimation to reduced salinity and alkalinity.

Alcolapia grahami is a unique ureotelic tilapia that lives in the highly alkaline, saline Lake Magadi, Kenya (pH, approximately 10.0; alkalinity, approximately 380 mmol L(-1); Na(+), approximately 350 mmol L(-1); Cl(-), approximately 110 mmol L(-1); osmolality, approximately 580 mosm kg(-1)). The fish survived well upon gradual exposure to dilute lake water (down to 1%, essentially freshwater). Urea excretion continued, and there was no ammonia excretion despite favorable conditions, indicating that ureotelism is obligatory. Levels of most ornithine-urea cycle enzymes in the liver were unchanged relative to controls kept for the same period in 100% lake water. The fish exhibited good abilities for hypo- and hyperregulation, maintaining plasma Na(+), Cl(-), and osmolality at levels typical of marine and freshwater teleosts in 100% and 1% lake water, respectively. Plasma total CO(2) did not change with environmental dilution. Routine oxygen consumption (Mo(2)) was extremely high in 100% lake water but decreased by 40%-68% after acclimation to dilute lake water. At every fixed swimming speed, Mo(2) was significantly reduced (by 50% at high speeds), and critical swimming speed was elevated in fish in 10% lake water relative to 100% lake water. Osmotic and Cl(-) concentration gradients from water to plasma were actually increased, and osmotic and Na(+) gradients were reversed, in 10% and 1% dilutions relative to 100% lake water, whereas acid-base gradients were greatly reduced. We suggest that approximately 50% of the animal's high metabolic demand originates from the cost of acid-base regulation in the highly alkaline Lake Magadi. When this load is reduced by environmental dilution, the energy saved can be diverted to enhanced swimming performance.

Adaptation, Physiological↗

Discordance between genetic structure and morphological, ecological, and physiological adaptation in Lake Magadi tilapia.

The Magadi tilapia (Alcolapia grahami, formerly Oreochromis alcalicus grahami) is a remarkable example of teleost life in an extreme environment. Typical conditions include water pH=10, titration alkalinity>300 mM, osmolality=525 mOsm, temperatures ranging from 23 degrees to 42 degrees C, and O(2) levels fluctuating diurnally between extreme hyperoxia and anoxia. A number of relatively small tilapia populations are present in various thermal spring lagoons around the margin of the lake separated by kilometers of solid trona crust (floating Na(2)CO(3)) underlain by anoxic water. Despite the apparent isolation of different populations, annual floods may provide opportunities for exchange of fish across the surface of the trona and subsequent gene flow. To assess the question of isolation among Lake Magadi populations, we analyzed the variable control region of the mitochondrial DNA (mtDNA) from six lagoons. A total of seven mtDNA haplotypes, including three common haplotypes, were observed in all six populations. Several of the Lake Magadi populations showed haplotype frequencies indicative of differentiation, while others showed very little. However, differentiation among lagoon populations was discordant with their geographical distribution along the shoreline. All populations exhibited the unusual trait of 100% ureotelism but specialized morphological and physiological characteristics were observed among several of the lagoon systems. In addition, distinct differences were observed in the osmolality among the lagoons with levels as high as 1,400-1,700 mOsm kg(-1), with corresponding differences in the natural levels of whole-body urea. These levels of osmotic pressure proved fatal to fish from less alkaline systems but remarkably were also fatal to the fish that inhabited lagoons with this water chemistry. Upon more detailed inspection, specific adaptations to differential conditions in the lagoon habitat were identified that allowed survival of these cichlids. Additional evidence against potential for gene flow among lagoons despite the sharing of common mtDNA haplotypes was that the osmolality of floodwaters following a heavy rain showed lethal levels exceeding 1,700 mOsm kg(-1). In isolation, different mtDNA haplotypes would be predicted to go to fixation in different populations due to rapid generation times and the small effective population sizes in a number of lagoons. We propose a model of balancing selection to maintain common mtDNA sequences through a common selection pressure among lagoons that is based on microhabitats utilized by the tilapia.

Adaptation, Biological↗